Specific host translation perturbations promote Tn Smu 1 loss independently of the canonical ImmA regulator.

Integrative and conjugative elements (ICEs) are major drivers of horizontal gene transfer and bacterial genome evolution. Although ICE-encoded regulatory circuits have been extensively characterized, the impact of host physiology on the stability of integrated ICEs remains poorly understood. Here, we identify a host-dependent pathway that links specific host translation perturbations to loss of the ICE Tn Smu1 in Streptococcus mutans . Analysis of host-gene deletion mutants revealed that disruption of fmt , rnjA , or rnjB -three translation-associated host genes-reproducibly promoted Tn Smu1 loss through a mechanism that bypasses the canonical ICE-encoded metalloprotease ImmA but remains dependent on the native attachment site attR . This phenotype was selective, as mutations affecting other essential cellular functions, including protein folding, tRNA modification, cell division, and fatty acid biosynthesis, failed to destabilize Tn Smu1 despite undergoing the same experimental evolution and accumulating adaptive genomic changes. Preventing Tn Smu1 loss in these translation-associated mutants markedly reduced bacterial growth, whereas loss of the element improved fitness, indicating that ICE elimination alleviates the cost associated with Tn Smu1 retention under these conditions. Finally, we show that the relationship between host translation and Tn Smu1 stability extends to a genetically distinct S. mutans clinical isolate, although with strain-dependent penetrance. Together, these findings identify host translational state as an important physiological determinant of Tn Smu1 stability and reveal that bacterial hosts can influence the maintenance of integrated mobile genetic elements through mechanisms that extend beyond element-encoded regulatory circuits.